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Histone deacetylase inhibitors—turning epigenic mechanisms of gene regulation into tools of therapeutic intervention in malignant and other diseases

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Abstract

Histone deacetylase inhibitors reside among the most promising targeted anticancer agents that are potent inducers of growth arrest, differentiation, and/or apoptotic cell death of transformed cells. In October 2006, the US Food and Drug Administration approved the first drug of this new class, vorinostat (1, Zolinza, Merck). Several histone deacetylase (HDAC) inhibitors more are in clinical trials. HDAC inhibitors have shown significant activity against a variety of hematological and solid tumors at doses that are well tolerated by patients, both in monotherapy as well as in combination therapy with other drugs. This paper reviews the most recent developments in HDAC inhibitor design, particularly in the context of anticancer therapy, and other possible pharmaceutical applications.

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Acknowledgment

This work was supported in part by the grant from BioFuture 0311852 from the Bundesministerium für Forschung und Technologie, Germany, and Human Frontier Science Program (HFSP) grant RGY56/2004. The authors are grateful to colleagues in the field for sharing valuable information, in particular, T. Beckers, R. Ficner, S. Guccione, M. Jung, A. Kuhn, F.-J. Meyer-Almes, R. Schneider, D. Wegener, H. Weinmann, and O. Witt. A.S. thanks K. Schwienhorst and the staff at the FSZ Hannover for critically reading the manuscript. A.S. also would like to thank all his coworkers for many years of fruitful research and a friendly atmosphere.

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  1. Department of Molecular Genetics and Preparative Molecular Biology, Institute for Microbiology und Genetics, Grisebachstr. 8, 37077, Göttingen, Germany

    Daniel Riester, Christian Hildmann & Andreas Schwienhorst

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  1. Daniel Riester
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  2. Christian Hildmann
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  3. Andreas Schwienhorst
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Correspondence to Andreas Schwienhorst.

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Riester, D., Hildmann, C. & Schwienhorst, A. Histone deacetylase inhibitors—turning epigenic mechanisms of gene regulation into tools of therapeutic intervention in malignant and other diseases. Appl Microbiol Biotechnol 75, 499–514 (2007). https://doi.org/10.1007/s00253-007-0912-1

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  • DOI: https://doi.org/10.1007/s00253-007-0912-1

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